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2010年9月23日

[News] Medical Plastics Industry Set for Expansion over the Next Decade

The medical plastics industry is set to expand rapidly over the next decade taking up increasing proportions of GDP, as countries provide healthcare to an ageing population, access to medicine expands in developing regions and new technology is developed. Some of the issues in using polymers in medicine were debated at the latest AMI conference on Medical Grade Polymers, which took place September 14-15, 2010 in Philadelphia, USA.

The quality controls in place in the medical device industry are stringent for reasons of patient safety. The whole industry relies on timely communication between suppliers and manufacturers. For example, under FDA regulations if there is a change in manufacturing or polymer supplier then the situation must be notified and re-evaluated. If the change is regarded as significant then more testing may need to be undertaken, which can delay or halt production of a device. Most manufacturers require around a 2-year lead time for a change of polymer. Last year's economic crisis left some companies in a difficult situation when suppliers entered Chapter 11 proceedings or stopped supplying their approved materials.

Vistakon, a supplier of contact lenses and part of the Johnson & Johnson group, is rigorous in its procurement of medical polymers. The company considers qualifying alternate suppliers in case of unexpected failure. One of the big issues is the cost of qualification and the company starts its process with a complete quality audit of a potential supplier. There is an FDA 30-day notice procedure for registering an "Alternate Qualified Supplier of a Critical Material", however if the data submitted is incomplete this can be extended from 6 months onwards.

Monitoring shelf-life of polymers is important for performance. Boston Scientific conducts a variety of tests to check materials for suitability for purpose, and puts safety measures in place. For example, there can be variations in molecular weight distribution affecting overall properties. Tests for material performance include gel permeation chromatography (GPC) for molecular weight, capillary rheometry for viscosity, melt flow index for ease of flow, differential scanning calorimetry (DSC) for thermal transitions and qualitative analysis, and Fourier Transform Infrared Spectrometry (FTIR) for contamination and identification. Many factors can affect materials including transport and storage conditions: as one example, polyamide is moisture sensitive. In another instance a warning was issued that handling the material with propane-powered forklifts could give it a pink color. Boston Scientific puts patient safety at the top of design priorities, together with comfort and ease of use for physicians. Cost effectiveness is becoming a big factor in current development. In some company takeovers a legacy device, which is not going to be developed further, is bought as part of the deal so the existing materials will be kept in use. There is no value to the company in this instance in expensive validation of new suppliers.

Clariant International Masterbatc h Business Unit has been reviewing its place in the healthcare markets due to the risks of brand damage if problems arise, and has moved to a more rigorous approach. The specialist knowledge-base for this industry is now focused in 3 locations in USA, Europe and Asia, all of which are ISO13485 certified. Color is being used in the industry for aesthetic and safety purposes. For example, different doses or types of drug containers can be color-coded. The home healthcare market is expanding as patients receive medical support locally for convenience and to relieve the load on the hospital system: this is leading to more stylish casings and visible components.

For commodity polymer companies such as Basell Polyolefins, a LyondellBasell company, the volumes required by the medical industry are very small so it is not practical to set aside whole plants just for that purpose. It would be impractical to set up clean room procedures for a site covering 3-4 square miles. There are variations in polyolefins from the use of different synthesis methods such as metallocene versus Ziegler-Natta catalysts, which give different grades with different molecular weight distribution and combination with different additives. All of these factors can significantly affect the properties of the polymers. Hence LyondellBasell has developed the Purell specialty healthcare grades.

Engineering and high performance plastics are supplied to the medical markets by companies like SABIC Innovative Plastics. In line with many other polymer suppliers, applications are limited to less than 29 days body exposure, because the long-term implant industry is relatively high risk in terms of liability. SABIC polycarbonate blends have been used in thin wall injection molded housings and polyetherimide in subcuticular skin staplers, as two examples. The European regulations on Restriction of Hazardous Substances (RoHS) are now affecting healthcare, for example where lead is used in radiation shielding. Specialty compounds can be used to replace lead.

Biodegradable plastics have a role in temporary medical devices providing a function until the body is able to recover, for example in tissue scaffolding. ELLA-CS in the Czech Republic is using polydioxanone in gastrointestinal and tracheobronchial stents to maintain a patent lumen: gradual hydrolysis of the device removes it without surgical intervention.

Meditech Medical Polymers has been working with next generation UHMWPE. In the past the material did not contain stabilisers or processing aids. Now a few antioxidants have been approved for use including Vitamin E (alpha tocopherol). The stabilized material needs light barrier packaging and there is increased potential for inclusions, color variation and cross-contamination. However it offers reduced degradation and maintenance of mechanical properties. It is very expensive to change a material and the supplier and device manufacturer have to agree who is taking responsibility. Again, communication is key.

The Neuromodulation division at Boston Scientific is involved in production of stimulation leads, enclosures with feedthroughs, and biocompatibility analysis. Polyurethane is used in pacing and NeuroStim leads, based on polyether PU. In the 1980s there were problems with the PU insulation of pacing leads caused by giant cells in the body releasing lysozyme, which in turn gives rise to free radicals, causing environmental stress cracking. Since that time, PU chemistry for implants has been improved by reducing the amount of soft domain and cutting the potential for hydrolytic cleavage. However, if a device is improperly installed leading to tensile stress, for example by using a very tight suture, then issues can still arise: a suture sleeve can protect against this occurrence.

Aortech Biomaterials supplies PU with polydimethyl siloxane (PDMS) soft segments, which are more biostable and have good oxidative stability. This is currently in use in over 1 million pacemakers and defibrillators, as biliary and urinary stent coatings, and in cardiac and pulmonary cannula applications. Carbonate can be introduced into the PDMS to increase polarity and give lower hardness with high tensile properties.

Thermoplastic PU (TPU) is supplied by Lubrizol Advanced Materials: the business was acquired from BF Goodrich. The ISOPLAST grade has a flexural modulus up to 2,200,000psi and very good low temperature impact properties. It can be colored with masterbatch and is being used as metal replacement. It has excellent chemical resistance and has been tested with hospital disinfectants such as bleach and glutaraldehyde. It can be sterilized using ethylene oxide, gamma and electron beam irradiation. This TPU can be extruded into film with good barrier properties to oxygen. Impact modified ISOPLAST is being used in applications such as ultrasound paddle handles and flexible joints with thin walls. A glass-reinforced grade was used as metal replacement in an abdominal retractor where the number of parts was reduced from 49 to 8 and the risk of cuts from the sharp metal was eliminated.

The body is one of the most hostile environments for materials and hence ultra high performance plastics have a role. Evonik Industries is producing new VESTAKEEP PEEK for medical devices, launched in 2009 for permanent implants. It has a Master File with the FDA for devices and will assist manufacturers.

Oxford Performance Materials produces one of the ultimate performance plastics, polyether ketone ketone (PEKK), and production is planned to increase in the US and France as the company has been acquired by Arkema. PEKK can be amorphous or crystalline and has good chemical resistance, high mechanical properties and excellent electrical resistance. Density is similar to cortical bone. In some situations it can be applied as a melt giving good adhesion. The amorphous material has been used in a cranial clip; it is also thermoformable. There are OsteoFab grades for digital manufacturing.

DuPont Performance Polymers supplies polymers to the medical market for general healthcare applications and those involving brief or temporary (no more than 29 days) implantation. The company's healthcare products include PBT, PET, POM, polyamide, and some elastomers. The company is developing these materials from renewable sources as well. One example of use is the Niagara foot developed in Toronto for victims of landmines, which requires low flexural fatigue, high stress resistance, high flow for manufacturing thick parts, excellent impact properties, and storage and release of energy. Hytrel TPC-ET, a thermoplastic polyester elastomer, was used in this project and the device was tested to 2 million cycles (twice the strides of an average adult per year), over 3330N heel load and over 2790N for toe loads.

Tritanfrom Eastman Chemical has been tested for medical applications using a variety of procedures. It performs well under irradiation and ethylene oxide sterilization including good color stability. It is close to polycarbonate in toughness (Notched Izod test) and has been tested for chemical resistance to lipids and strong disinfectants. It is currently being tested for use in a new wireless monitoring device worn on the arm.

Parylene coatings provide excellent chemical resistance and this is attracting attention from other industries including aerospace. Specialty Coating Systems provides these vapor phase polymers for medical devices. They are para-xylylene based molecules and provide a chemical, moisture and fluid barrier between the body and the device, as well as being biocompatible. The material is vaporized, pyrrolysed and deposited. In a new development, the company is also making tiny devices from this material by deposition, such as an intraocular pressure sensor based on a spiral tube, and micro cortical implants with a cable and shanks which are completely flexible.

The effects of gamma irradiation, electron beam and ethylene oxide sterilization on silicone rubber have been studied by Saint-Gobain Performance Plastics. It is widely used in medical devices due to its biocompatibility and purity. Liquid silicone rubber, platinum cured high consistency rubber (HCR) and the more rigid peroxide cured HCR were all examined. Both gamma and electron beam treatment lead to a rise in tensile modulus and a reduction in tensile elongation and tear strength. Ethylene oxide had minimal effects on the physical properties.

Sterilization procedures are designed to kill pathogens such as bacteria and fungi, however there can still be problems with chemical and particulate contaminants on medical devices, which are not removed by these methods. The Cambridge Polymer Group is working on such cleanliness issues for medical devices. The first case study was carried out for Sulzer Orthopedics, which noticed poor tissue ingrowth with a particular batch of titanium acetabular shell hip devices. The problem was tracked to a pyrogen contaminant, and after examining manufacturing facilities the source was found to be endotoxins in the sump water of a machine shop. Devices cleaned by nitric acid passivation did not show the same level of problems. Cambridge Polymer Group is now looking at methods of identifying substances on explants as a way of finding the sources of failure using techniques such as FTIR and gas chromatography-mass spectrometry (GCMS).

New materials can take a long time to develop. Altrika has adopted chemical synthesis technology from the pharmaceutical industry, High Throughput Combinatorial Chemistry, for rapid polymer research. The in-house library comprises over 2,000 polymers including blends of biodegradable plastics. Materials are formed and deposited in a microarray glass slide containing 100 different plastics. The slide is dried and tested, for example, for adhesion to different types of cell lines. The company has been involved in developing a corneal bandage to promote growth of replacement epithelial cells with Moorfields Eye Hospital. It is working on blood filtration polymer coatings to selectively remove white cells. A third product is Myskin, which is a proprietary cell delivery membrane for wound cover.